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Let’s look at a randomized trial for medication treatment in autism, the BAART trial—that is, biomarkers in autism of aripiprazole and risperidone treatment. This trial was published in 2019 in the Journal of Pharmacotherapy.
Before diving into these data on risperidone and aripiprazole, let’s step back and look at the treatment of autism spectrum disorder overall. There are several targeted psychotherapies for ASD. The principal among them is ABA, which is applied behavior analysis. According to a 2016 review of all treatments for autism spectrum disorder by Karen Wagner and her colleague, Melissa DeFilippis, there is also PRT, pivotal response treatment. Those are the 2 main psychotherapies for the autism spectrum (ASD), PRT, and ABA. Both of these are very behavioral approaches.
According to Dr. DeFilippis and Dr. Wagner’s review, it does not appear that there had been any head-to-head studies of these therapies vs pharmacotherapy or even medication studies that use a psychotherapy control group. Instead, in their review, there is a remarkable list of medications studied in randomized trials in ASD, including antipsychotics, antidepressants, mood stabilizers, stimulants, and 9 others in randomized trials. Also, another 8 different medications have been studied as augmentation for risperidone. Interestingly, all but buspirone were superior to placebo as augmentation agents. So, there is a vast range of medications that have been examined for various aspects of ASD.
The BAART trial compares the 2 main treatments for irritability that have emerged from all those randomized trials, which are risperidone and aripiprazole. These are the 2 that have FDA indications where nothing else does. That does not mean they are better. It just means that those are the ones that someone went to the trouble of getting an FDA indication for. The question then is, where to start if using a medication for irritability in ASD? The BAART trial looked not just efficacy but at a whole range of side effects to help facilitate making this choice. The subjects here were 6-to-15 years old, average around 8.
The results showed a significant weight gain. Twenty-six percent of the aripiprazole group gained more than 7% of their body weight. For risperidone, it was 70%. One of the reasons these numbers are so high is that participants were selected for having no previous exposure to weight-gaining medications, like antipsychotics. So, they did not start from already having metabolic problems. Also, the authors found that prolactin increased from a mean of 9 before treatment to 40 on risperidone, with no increase in the aripiprazole group. There were no major differences in efficacy. Both treatments produced substantial improvement, which steadily increased during the 22-week center study.
The other differences of note were sedation in 23% of the aripiprazole group vs only 7% for risperidone. Moreover, there were no differences in agitation or akathisia. So, what doses were these children getting? For aripiprazole, the starting dose was 2 mg. Roughly half the subjects ended up on 2 mg or 5 mg and the other half on 10 mg. For risperidone, roughly a third were on 0.5 mg or 1 mg, a third on 1.5 mg, and the remaining third on 2 mg, with a few outliers at 2.5 mg and 3 mg. The authors point out that 25% of the patients in the aripiprazole group and 33% of the patients in the risperidone group stuck with the lowest dose.
In conclusion, for irritability in autism spectrum disorder, the authors do not emphasize choosing aripiprazole over risperidone. However, given roughly equal efficacy and aripiprazole’s lower incidence of significant weight gain and lack of prolactin increases, it looks like a better starting place. Nevertheless, a comparison with a therapy like applied behavioral analysis would be helpful.
Abstract
Pharmacotherapy of Autism Spectrum Disorder: Results from the Randomized BAART Clinical Trial
C Lindsay DeVane, Jane M Charles, Ruth K Abramson, John E Williams, Laura A Carpenter, Sarah Raven, Frampton Gwynette, Craig A Stuck, Mark E Geesey, Catherine Bradley, Jennifer L Donovan, Alicia G Hall, Shelley T Sherk, Nancy R Powers, Eve Spratt, Anne Kinsman, Markus J Kruesi, John E Bragg Jr
The objective of this trial, Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART), was to provide support and guidance for an evidence-based approach for the selection and monitoring of initial pharmacotherapy in patients with autism by assessing predictors of efficacy, tolerability, and safety. This randomized double-blind parallel-group study was conducted in three academic medical centers and a single private pediatric practice. Eighty children or adolescents (aged 6-17 yrs) with autistic disorder were enrolled, and 61 patients were randomized to the study drug. Of those patients, 51 completed the 10-week trial, and 31 completed an optional 12-week blinded extension phase. All patients were treated with 2 weeks of placebo before random assignment to receive aripiprazole (31 patients) or risperidone (30 patients) for 10 weeks. Sixteen placebo responders (20%) were excluded from further analysis. Drug dosing followed U.S. Food and Drug Administration (FDA) labeling, and weekly dosage adjustments were allowed until week 4; patients were then maintained on a fixed dose for 6 additional weeks. Safety, physical, and psychological assessments were recorded weekly or every 2 weeks. No significant differences in severity of illness between the aripiprazole and risperidone groups were noted at baseline. All patients significantly improved on the Aberrant Behavior Checklist-Irritability subscale after 1 week and continued for the remaining 9 weeks and the extension phase. Improvement was greatest in the risperidone group at every assessment period and was statistically significantly better than that in the aripiprazole group at weeks 3 and 6 (p<0.05). No dose-limiting adverse events occurred during the dose-titration period. Mean weight gain in the aripiprazole group was significantly less than that in the risperidone group at week 4 (0.62 vs 1.38 kg, p=0.033) and week 10 (1.61 vs 3.31 kg, p<0.001), but the difference became nonsignificant for the 31 patients completing the 3-month extension phase (4.36 vs 5.55 kg, p=0.26). Pharmacotherapy of patients with autism spectrum disorder resulted in behavioral improvement within 1 week and lasted at least 22 weeks. Weight gain occurred to a greater degree with risperidone than aripiprazole initially, but the differences became nonsignificant by the end of the trial. Our trial supports previous results of drug efficacy and safety in patients with autism spectrum disorder from other trials and extends the evidence-based support for choosing an FDA-approved drug for initial pharmacotherapy for autism spectrum disorder.
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Reference
DeVane, C. L., Charles, J. M., Abramson, R. K., Williams, J. E., Carpenter, L. A., Raven, S., Gwynette, F., Stuck, C. A., Geesey, M. E., Bradley, C., Donovan, J. L., Hall, A. G., Sherk, S. T., Powers, N. R., Spratt, E., Kinsman, A., Kruesi, M. J., & Bragg, J. E. (2019). Pharmacotherapy of autism spectrum disorder: Results from the randomized BAART clinical trial. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 39(6), 626-635.
